It has been proposed that the interaction of hemoglobin with erythrocyte membranes has important physiological and pathological implications. An equilibrium competitive binding assay has been developed using reductive methylation to tritiate hemoglobin. We have found that in vitro binding is only detectable under non-physiological conditions, i.e. very low pH or ionic strength. It is possible that under the non-ideality conditions in the erythrocyte that some interaction occurs; however, experimental or theoretical demonstration of this remains to be accomplished.